Neoplasms

All Conditions

Symptoms and General Pathology

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Recurrence

Thyroid Neoplasms

Thyroid Diseases

Thyroid Cancer, Papillary

Leukemia-Lymphoma, Adult T-Cell

Adenocarcinoma, Follicular

Carcinoma, Papillary

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Adult T-cell Leukemia/lymphoma

Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib S-malate

Laboratory Biomarker Analysis

Manisha Shah

This phase II trial studies how well cabozantinib-s-malate works in treating patients with thyroid cancer that does not respond to treatment. Cabozantinib-s-malate may stop the growth of thyroid cancer by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of thyroid cancer by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. The objective response rate, defined as the proportion of patients who have had a partial response (PR) or complete response (CR) within the first 6 months after initiation of therapy with cabozantinib (cabozantinib-s-malate).

SECONDARY OBJECTIVES:

I. To assess duration of objective response, progression-free survival and overall survival.

II. To assess tolerability and adverse events of cabozantinib as a 2nd line therapy in patients with differentiated thyroid cancer (DTC).

TERTIARY OBJECTIVES:

I. To assess effect of cabozantinib on serum tumor marker thyroglobulin and its correlation with overall response rate.

II. To assess response of cabozantinib in bone metastasis (bone metastasis-specific progression free survival) as evaluated by pre- and on-study functional imaging such as bone scan, fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scan and/or 18F sodium fluoride (NaF) PET scan.

III. To assess effect of cabozantinib on serum and urinary markers of bone turnover and its correlation with response to bone metastasis.

IV. To assess predictors of response by performing tumor genotype studies (e.g. v-raf murine sarcoma viral oncogene homolog B \[BRAF\], rat sarcoma \[RAS\], phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha \[PIK3CA\], mitogen-activated protein kinase 1 \[MAP2K1\], v-akt murine thymoma viral oncogene homolog 1 \[AKT1\], mesenchymal-epithelial transition \[MET\], rearranged in transformation \[RET\]/papillary thyroid carcinoma \[PTC\] rearrangement) in archived tumor tissue.

V. To assess predictors of response by assessing baseline expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor (pVEGFR), phosphorylated mitogen-activated protein kinase 1 (pERK), phosphorylated AKT1 (pAKT) and/or total met proto-oncogene (MET) by immunohistochemistry in archived tumor tissue.

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3 months for 1 year.

Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

Phase II Study of Cabozantinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer Who Progressed on Prior VEGFR-Targeted Therapy

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

These baseline levels will be quantitatively summarized and graphically explored, in particular in terms of how they relate to clinical outcomes of interest. Analyses exploring differences in these angiogenic and correlative markers in relation to clinical outcomes will be largely hypothesis-generating. With limited numbers of patients patterns of difference will primarily be looked for using graphical analyses; these can include plots of these marker levels in relation to clinical outcomes to identify potential patterns of interest.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Tolerability of the regimens will be assessed through assessing the number of patients who required dose modifications and/or dose delays. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.

Side-by-side boxplots will be used to assess possible differences in this change between responders and non-responders, and scatterplots can assess the influence of baseline thyroglobulin levels on these measures of change.

Exelixis

National Cancer Institute (NCI)

The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.

Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib S-malate: Given PO

Laboratory Biomarker Analysis: Correlative studies

Treatment (Cabozantinib-s-malate)

Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Manisha Shah, MD

Objective Response Rate, Defined as the Proportion of Patients Who Have Had a PR or CR as Assessed by the RECIST Version (v)1.1

Data not collected to be analyzed at this time

Bone Turnover, as Measured by Serum and Urinary Markers of Bone Turnover

Duration of Objective Response as Assessed by the RECIST v1.1

Data has not been collected and analyzed at this time

Expression Levels of Predictive Biomarkers of Response by Immunohistochemistry in Archived Tumor Tissue

Genotype of Biomarkers Potentially Predictive of Response

Left ventricular systolic dysfunction

asymptomatic increased lipase

osteonecrosis of the jaw

decubitus ulcer

pneumonia

meningitis

perianal hidradenitis suppurativa

Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0

Overall Survival

Percent Change in Serum Tumor Marker Thyroglobulin Levels

Progression-free Survival

Response of Cabozantinib-s-malate in Bone Metastasis (Bone Metastasis-specific Progression Free Survival) as Evaluated by Functional Imaging

Overall Study

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.

Selumetinib

David Neil Hayes

This phase II trial is studying how well selumetinib works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Ascertain the objective response rate (complete response and partial response) in patients with iodine I 131-refractory papillary thyroid cancer treated with selumetinib.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this treatment in these patients. II. Determine the pharmacokinetic profile of this treatment in these patients. III. Determine the progression-free and overall survival of these patients. IV. Assess proxy measures of treatment response (thyroglobulin and PET scan) in patients treated with selumetinib.

IV. Compare relevant laboratory correlates between responders and non-responders.

OUTLINE: This is a multicenter study.

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Archived tissue is examined for gene mutations, including RET, BRAF, NTRK, and RAS, by fluorescence in situ hybridization and/or polymerase chain reaction and fluorescence melting curve analysis. Protein expression of ERK and phosphorylated ERK is assessed by immunohistochemical staining.

Blood samples are collected periodically for pharmacokinetic analysis and biomarker assessment (thyroglobulin and antithyroglobulin autoantibodies).

After completion of study therapy, patients are followed periodically for up to 2 years.

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

Phase 2 Study of Selumetinib Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements

ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.

PFS is defined as the duration of time from start of treatment to time of progression or death. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Secondary end points include toxicity, progression free survival, and overall survival. Due to the small sample size and absence of high quality historic data for this disease, these analyses were planned to be mostly exploratory and descriptive in nature.

Number of participants with related adverse events, per category and Grade category. Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Overall Survival using the Kaplan-Meier method with associated confidence intervals. OS analysis was intended to be mostly exploratory and descriptive in nature.

All participants were evaluated for adverse events.

All Participants

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer	NCT01811212	Poorly Differen... Recurrent Thyro... Stage I Thyroid... Stage I Thyroid... Stage II Thyroi... Stage II Thyroi... Stage III Thyro... Stage III Thyro... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro... Tall Cell Varia... Thyroid Gland O...	Cabozantinib S-... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine	NCT00559949	Recurrent Thyro... Stage I Thyroid... Stage II Thyroi... Stage III Thyro... Stage IV Thyroi...	Laboratory Biom... Selumetinib	18 Years -	National Cancer Institute (NCI)
Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine	NCT00559949	Recurrent Thyro... Stage I Thyroid... Stage II Thyroi... Stage III Thyro... Stage IV Thyroi...	Laboratory Biom... Selumetinib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage ii thyroid gland papillary carcinoma